Effects of acute a2 blockade on insulin action and secretion in humans.. Natali, Andrea, Amalia Gastaldelli, Alfredo Qui[circumflex]uones Galvan, Anna Maria Sironi, Demetrio Ciociaro, Giovanna Sanna, Pierre Rosenzweig, and Ele Ferrannini. Metabolism Unit of the C.N.R. Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa, Pisa, Italy, and Synth[umlaut]alabo Recherche, Paris.
APStracts 4:0201E, 1997.
We tested whether acute a2 blockade affects insulin secretion, glucose and fat metabolism, thermogenesis, and hemodynamics in humans. During a 5-hr epinephrine infusion (50 ng min-1kg-1) in 5 volunteers, deriglidole, a selective a2 receptor inhibitor, led to a more sustained rise in plasma insulin and C-peptide levels (+59 14 vs +28 6, and +273 18 vs +53 14 pmol l-1, p<0.01vs placebo) despite a smaller rise in plasma glucose (+0.90 0.4 vs +1.5 0.3 mmol l-1, p<0.01). Another 10 subjects were studied in the post-absorptive state and during a 4-hr hyperglycemic (+4 mmol l-1) clamp, coupled with the ingestion of 75 g of glucose at 2 hrs. In the post -absorptive state, hepatic glucose production, resting energy expenditure, plasma insulin, FFA and potassium concentrations were not affected by acute a2 blockade. Hyperglycemia elicited a biphasic rise in plasma insulin (to a peak of 140 24 pmol l-1) and C-peptide levels (1520 344 pmol l-1), and in insulin secretion (to 410 22 pmol min-1), the superimposed glucose ingestion elicited a further 2-fold rise in insulin and C-peptide levels and in insulin secretion. However, a2 blockade failed to change these secretory responses. Fasting blood -hydroxybutyrate and glycerol, and plasma FFA and potassium concentrations all declined with hyperglycemia; time-course and extent of these changes were not affected by a2 blockade. Resting energy expenditure (+25% vs +16%, p<0.01) and external cardiac work (+28% vs +19%, p<0.01) showed larger increments after a2 blockade. We conclude that acute a2 blockade in man (a) prevents epinephrine -induced inhibition of insulin secretion, (b) does not potentiate basal, intravenous- or oral glucose-induced insulin release, (c) enhances thermogenesis, and (d) increases cardiac work. 

Received 22 April 1997; accepted in final form 16 September 1997.
APS Manuscript Number E184-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997